研究报告
安洁然,陆林洁,蔡洁,丁书茂.低浓度甲醛促进K562细胞增殖的分子机制探究[J].环境科学学报,2018,38(1):416-424
低浓度甲醛促进K562细胞增殖的分子机制探究
- The molecular pathways of K562 cell proliferation promoted by low concentrations of formaldehyde
- 基金项目：国家自然科学基金面上项目（No.21577045）
- 作者
- 单位
- 安洁然
- 华中师范大学, 遗传调控与整合生物学湖北省重点实验室, 武汉 430079
- 陆林洁
- 华中师范大学, 遗传调控与整合生物学湖北省重点实验室, 武汉 430079
- 蔡洁
- 华中师范大学, 遗传调控与整合生物学湖北省重点实验室, 武汉 430079
- 丁书茂
- 华中师范大学, 遗传调控与整合生物学湖北省重点实验室, 武汉 430079
- 摘要：低浓度甲醛（Formaldehyde，FA）可以促进细胞增殖.本实验选用K562细胞为实验对象，用不同浓度的甲醛溶液处理细胞，探究其中可能存在的分子机制.测定细胞活力及胞内氧化损伤程度后，发现当甲醛浓度为75 μmol·L-1时，细胞增殖率上升（p < 0.05或p < 0.01），Warburg效应中的丙酮酸激酶M2型同工酶（PKM2）、葡萄糖转运蛋白1（GLUT1）、乳酸脱氢酶A（LDHA）、葡萄糖和乳酸含量上升（p < 0.05）；此外，细胞周期调控因子Cyclin D-cdk4与转录因子E2F1含量也上升（p < 0.05）.同时，细胞内氧化损伤加强，其中活性氧簇（reactive oxygen species，ROS）含量上升（p < 0.01），还原型谷胱甘肽（glutathione，GSH）下降（p < 0.05）.然而，在加入抗氧化剂VE后，氧化损伤程度减弱，细胞增殖率降低，PKM2、GLUT1、LDHA、葡萄糖、乳酸，Cyclin D-cdk4、E2F1含量均下降.结果表明低浓度甲醛可能通过氧化应激诱导Warburg效应和影响细胞周期调控因子两条途径促进细胞的增殖.
- Abstract：Previous studies have demonstrated that low concentrations of formaldehyde (FA) can promote cell proliferation. In the present study, K562 cells were exposed to different concentrations of FA, aiming to explore the underlying molecular pathway. The cell viability and levels of intracellular oxidative stress were both determined. As the data shown, 75 μmol·L-1 FA exposure increased the levels of cells proliferation rate (p < 0.05 or p < 0.01), as well as the levels of biomarkers involved in the Warburg effect including pyruvate kinase M2 isoenzyme (PKM2), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), glucose and lactic acid were all increased (p < 0.05). The contents of Cyclin D-cdk4 and transcription factor E2F1, as the regulated factors in cell cycle, were also improved (p < 0.05). Meanwhile, intracellular oxidative stress was enhanced:the contents of reactive oxygen species (ROS) increased (p < 0.01) while the contents of reduced glutathione (GSH) decreased (p < 0.05). However, with the addition of vitamin E, the oxidative damage and the cell proliferation rate were both decreased:the levels of PKM2, GLUT1, LDHA, glucose, lactate, Cyclin D-cdk4 and E2F1 were all reduced, indicating low concentrations of FA could promote the proliferation of cells through the Warburg effect and affecting cell cycle regulators mediated by oxidative stress.
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